Affordable HIV drug shows promise for improving vision in diabetic eye disease

Affordable HIV drug shows promise for improving vision in diabetic eye disease

A low-cost, long-approved HIV drug may improve vision in patients with a blinding complication of diabetes more effectively and at a much lower cost than many existing treatments, an initial clinical trial suggests. Additionally, the medication is taken orally, potentially giving patients an alternative to monthly injections directly into their eyes.

The drug, lamivudine, could provide an important new option for millions of patients with diabetic macular edema (DME), a condition that causes fluid to build up in the retina of the eye. It is estimated that approximately 1 in 14 people with diabetes develop sight-stealing eye disorder, and more than 37 million adults live with diabetes in the United States alone.

An oral medication that improves vision in DME would be a game changer because it would be more convenient for patients than frequent, often monthly, injections into the eye. The mechanism of action of lamivudine is also different from that of existing treatments, allowing us to also develop combination therapies. “

Jayakrishna Ambati, MD, researcher, founding director of the UVA Health Center for Advanced Vision Science

Diabetic macular edema (DME)

Ambati's collaborators at Brazil's Universidade Federal de São Paulo, led by Dr. Felipe Pereira and Dr. Eduardo Buchele Rodrigues, enrolled two dozen adults with DME in a small randomized clinical trial. Participants were randomly assigned to receive either lamivudine or a harmless placebo, in addition to injections of the drug bevacizumab in the eyes after four weeks.

Participants who received lamivudine showed significant improvements in vision even before their first eye injections. Their ability to read letters on an eye chart improved by 9.8 letters (approximately 2 lines on the eye chart) after four weeks, while participants who received placebo saw their ability decrease by 1.8 letters. One month after the bevacizumab injections, the lamivudine recipients had improved by a whopping 16.9 letters (more than 3 lines on the eye chart), while the placebo group that received bevacizumab alone had only increased by 5.3.

The results suggest that lamivudine may work both alone and in conjunction with bevacizumab injections, although larger studies are needed to support this, the researchers say. However, lamivudine alone could be life-saving for patients in many areas of the world with limited access to specialty doctors or monthly eye appointments, Ambati said.

“A $20 monthly or even cheaper oral pill that improves vision as much or more than eye injection therapy that costs up to $2,000 a month could be transformative for both patients and the health system,” he said.

Researchers believe that lamivudine is effective against DME because it blocks the activity of inflammasomes, important components of our immune system. Inflammasomes normally act as infection sensors but have also been implicated in the development of DME.

Ambati and his collaborators say future studies of lamivudine will need to enroll larger numbers of patients and follow them for longer than eight weeks. But researchers are encouraged by the promising signs for their first test. For example, they note that lamivudine improved vision not only in the first four weeks - when the greatest improvement is typically seen in DME - but also in the following four weeks.

“We have developed a safer version of lamivudine called K9 that blocks inflammasomes without the potential side effects of lamivudine,” said Ambati, the DuPont Guerry III Professor in the UVA School of Medicine Department of Ophthalmology. “So we are excited about the ongoing and planned clinical trials of K9 in DME.”

The new findings come hot on the heels of another discovery by Ambati suggesting that HIV drugs may significantly reduce the risk of Alzheimer's disease. His group previously found by analyzing large health insurance databases that the drugs, called nucleoside reverse transcriptase inhibitors, or NRTIS, may also reduce the risk of diabetes and macular degeneration.

The new DME clinical trial was inspired by similar findings and demonstrates the power of what Ambati calls “big data archaeology.”

Results published

Ambati and his colleagues have published their DME findings inMedCell Press' flagship clinical journal. The research team consisted of Felipe Pereira, Joseph Magagnoli, Meenakshi Ambati, Talita Fernandes de Oliveira, Juliana Angélica Estevão de Oliveira, Vinicius Oliveira Pesquero, Lucas Zago Ribeiro, Dante Akira Kondo Kuroiwa, Fernando Korn Malerbi, Sergio Atala Dib, Nilva Bueno Moraes, Michel Eid Farah, Eduardo Buchele Rodrigues and Jayakrishna Ambati. Jayakrishna Ambati is the co-founder of Iveena Holdings, Iveena delivery systems and Inflammasome therapeutics. A full list of authors' disclosures is included in the paper.

Ambati's research was supported by the National Eye Eye Institute and the National Institute on Aging of the National Institutes of Health, grants R01EY031039 and R01AG082748, and by UVA's Strategic Investment Fund, grant SIF167.

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